1. Field of the Invention
The present invention relates to automated sample preparation for scientific research and, more particularly, to user interfaces, methods, apparatus and articles of manufacture for performing automated preparation of biological assays and biological macromolecule purification.
2. Background of the Invention
In the field of molecular biology, there is an ever increasing number of uses for isolated biological macromolecules, such as DNA, RNA, and proteins. Isolated biological macromolecules may be used, for example, in identifying genetic defects, diagnosing diseases, development of new drugs or treatments, and studying gene expression. Purified nucleic acids are derived from biological material samples, such as whole blood, plasma, blood serum, urine, feces, saliva, sperm, tissue, cells, and other body fluids, materials, or plant tissue.
There are many known methods for extracting biological macromolecules from biological materials. In fact, a number of specialized techniques have been developed for isolation and purification of DNA and RNA from various cell lines and tissue types. Most isolation and purification protocols, however, involve combinations and variations of a few basic steps.
Generally, the first step of an isolation protocol is to harvest tissue or collect cells from the biological material sample. A small portion of the biological material is placed in a container, such as a test tube or well of a multi-well tray. The sample is mixed with a lysis buffer solution that causes the cell structure of the biological material to break down and dissolve. This process is known as lysing. The type of lysis buffer used will depend on many factors including the type of biological material, the specific isolation protocol, and how the resulting biological macromolecule will be used once it is isolated.
After lysing, DNA, RNA, and proteins may be isolated from the lysed-cell mixture by, for example, precipitation, centrifugation, filtration, or affinity complex. Isolation protocols may also require multiple iterations of one or a combination of these techniques. Separation of the desired biological macromolecule may require, for example, that the mixture be incubated. The biological macromolecule may be separated from the liquid forming a precipitate or "pellet." The remaining fluid can then be aspirated, or pipetted, from the vial or well leaving the biological macromolecule, or the macromolecule may be filtered from the remaining fluid. Once the macromolecule is isolated from the biological material, it often must be further purified to remove the effects of the lysing materials. Additionally, for some uses, the isolated macromolecule may be diluted. Examples of conventional RNA, DNA, protein isolation and purification protocols may be found in the Kaufman et al., Handbook of Molecular and Cellular Methods in Biology and Medicine, CRC Press, 1995, pp. 1-63, which is expressly incorporated herein by reference. These processes and other concepts of molecular biology are discussed in more detail in Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press (2.sup.nd Ed.), 1989, which is also expressly incorporated herein by reference.
The process of obtaining samples of DNA, RNA, and proteins in sufficient quantity for testing is a complicated and time intensive process. One experiment often requires the preparation of hundreds of samples, each of which may be prepared using slightly different control parameters. Historically, lab technicians have prepared trays or plates of multiple samples manually. A tray or plate may have any number of wells (eg. 12, 24, 48, 384, etc.) arranged in any configuration, however, a tray or plate having 96 vials or wells arranged in a 12.times.8 rectangular array is one popular arrangement. For each tray prepared, lab technicians must carefully record the exact, independent process used to prepare each of the wells.
The manual preparation of multi-well trays is therefore extremely tedious and, consequently, there have been numerous attempts to automate the process. Many manufacturers provide robotic devices for laboratory automation. These robotic devices frequently are pre-programmed to perform only a handful of specific functions and must be reprogrammed to perform other functions.
One automated laboratory workstation is the Biomek.RTM. 2000 Workstation by Beckman Instruments. The Biomek 2000 workstation is a liquid handling device controlled by using a Windows-based software interface called BioWorks.TM.. BioWorks allows the user to adjust pipetting specifications for the liquid handling tools or customize a tool for a special liquid transfer function. The Biomek 2000 workstation, however, requires the user either to use a provided protocol, or to custom develop an assay protocol by explicitly specifying all decisions and adjustments of a pipetting action well in advance of the activity. The user is not guided by the system when creating protocols or choosing protocol parameters. Additionally, the Biomek 2000 workstation does not create a database of parameters used by the technician or allow the technician to recall previously used parameters associated with an individual sample. Furthermore, the Biomek 2000 workstation does not perform cross-checking of parameters input by a user.
Other conventional products, like the BioRobot.TM. 9600 and 9604 Systems by Qiagen.RTM., Inc., perform some automated liquid-handling tasks and purification protocols. These products, however, are designed to perform only a few of preprogrammed protocols at a time and are designed to prepare only one tray at a time. Following the completion of a protocol, a lab technician must manually remove or reposition the tray and reset the product to perform a secondary protocol. There is no cross-checking of parameters from one protocol to the next or between multiple trays.
Some conventional automated workstations allow users to create new protocols or modify existing protocols by modifying the parameters of, for example, type or quantity of liquid, length (in time) of incubation or mixing, or temperature of incubation. These conventional automated workstations do not, however, cross-check the parameters with a list of parameters recommended for specific parameters and therefore they allow the user to enter in parameters that may be in error. These modifications are done without any context to the desired protocol, such as prompting the user to enter parameters appropriate for the protocol. Furthermore, these conventional systems do not allow a user to easily specify different parameters for each separate well in a multi-well tray.
The increased use of isolated RNA, DNA, and proteins has created a need for automated methods for preparing sample trays and isolating DNA, RNA and proteins from biological materials samples that allow performance of multiple protocols in a sequence. There exists a need for an automatic workstation that allows for the rapid development of new protocols by focusing on the desired output of one or more protocols and not the individual steps required to achieve the desired output. There exists a further need for an automated workstation that allows for performance of multiple protocols on multiple trays. There exists a still further need for an intelligent automated workstation that helps avoid error by cross-checking parameters between multiple protocols in a sequence. There also exists a need for an automated workstation that allows a user to establish parameters for each vial or well in a multi-well sample tray.